Risk factors for failing to complete gemcitabine-cisplatin neoadjuvant chemotherapy in muscle invasive bladder cancer patients.

PURPOSE: We evaluated the risk factors associated with failure to complete gemcitabine-cisplatin (GP) neoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer (MIBC). MATERIALS AND METHODS: In total, 231 patients with MIBC treated with NAC before undergoing radical cystectomy between 2013 and 2022 participated in this study. Logistic regression analysis was performed to assess the relationship between the likelihood of incomplete NAC and clinical and demographic variables, including age, sex, hypertension (HTN), diabetes mellitus (DM), prechemotherapy glomerular filtration rate, clinical T stage, clinical N stage, and body mass index (BMI). RESULTS: Of 231 patients, 209 (90.5%) and 22 (9.5%) completed and discontinued the NAC course, respectively. The mean age was 66.13±9.15, 65.63±9.07, and 70.86±8.66 years for the total sample, continuation, and discontinuation groups, respectively (p=0.010). No significant inter-group differences in sex, HTN, height, weight, BMI, pre-chemotherapy glomerular filtration rate, clinical T stage, or clinical N stage were observed. According to the results of the multivariable analysis, age (odds ratio [OR] 1.076, 95% confidence interval [CI] 1.013-1.143, p=0.018) and the presence of DM (OR 2.541, 95% CI 1.028-6.281, p=0.043) were significantly associated with NAC discontinuation. CONCLUSIONS: Thus, older age and presence of DM are potential risk factors for GP NAC discontinuation in patients with MIBC. Further studies are required to validate our findings and develop strategies to minimize the rate of GP NAC discontinuation in this population.

Prostate cancer therapy using immune checkpoint molecules to target recombinant dendritic cells.

PURPOSE: We developed immune checkpoint molecules to target recombinant dendritic cells (DCs) and verified their anti-tumor efficacy and immune response against prostate cancer. MATERIALS AND METHODS: DCs were generated from mononuclear cells in the tibia and femur bone marrow of mice. We knocked down the programmed death ligand 1 (PD-L1) on monocyte-derived DCs through siRNA PD-L1. Cell surface antigens were immune fluorescently stained through flow cytometry to analyze cultured cell phenotypes. Furthermore, we evaluated the efficacy of monocyte-derived DCs and recombinant DCs in a prostate cancer mouse model with subcutaneous TRAMP-C1 cells. Lastly, DC-induced mixed lymphocyte and lymphocyte-only proliferations were compared to determine cultured DCs' function. RESULTS: Compared to the control group, siRNA PD-L1 therapeutic DC-treated mice exhibited significantly inhibited tumor volume and increased tumor cell apoptosis. Remarkably, this treatment substantially augmented interferon-gamma and interleukin-2 production by stimulating T-cells in an allogeneic mixed lymphocyte reaction. Moreover, we demonstrated that PD-L1 gene silencing improved cell proliferation and cytokine production. CONCLUSIONS: We developed monocyte-derived DCs transfected with PD-L1 siRNA from mouse bone marrow. Our study highlights that PD-L1 inhibition in DCs increases antigen-specific immune responses, corroborating previous immunotherapy methodology findings regarding castration-resistant prostate cancer.

Association of preoperative sarcopenia with the long-term prognosis of patients with bladder cancer undergoing radical cystectomy.

PURPOSE: This retrospective study aimed to assess the correlation between preoperative sarcopenia and long-term oncologic outcomes in patients undergoing radical cystectomy for bladder cancer. METHODS: We included 528 patients who underwent radical cystectomy for bladder cancer between 2000 and 2010 at Asan Medical Center, Seoul, Korea. Preoperative skeletal muscle mass was quantified by analyzing computed tomography images at the third lumbar vertebra. Sarcopenia was defined based on the skeletal muscle index. We evaluated various clinical and pathological factors to analyze the association between sarcopenia and long-term oncologic outcomes. RESULTS: The median follow-up time was 104 months. Sarcopenia was identified in 37.9% of the patients. Although no significant differences were observed in traditional pathological factors between the sarcopenic and non-sarcopenic groups, sarcopenia was significantly associated with worse oncologic outcomes. Compared to the non-sarcopenic groups, the sarcopenic group had lower overall survival rates (52.0% vs. 67.1% at 5 years, 35.5% vs. 52.7% at 10 years) and higher cancer-specific mortality (63.3% vs. 74.3% at 5 years, 50.7% vs. 67.4% at 10 years). Multivariable Cox regression analysis demonstrated that sarcopenia was an independent predictor of cancer-specific survival (hazard ratio: 1.49, 95% confidence interval: 1.11-2.01, p = 0.008), alongside body mass index, tumor stage, lymph node metastasis, and lymphovascular invasion. CONCLUSION: Sarcopenia was significantly associated with poor cancer-specific survival in patients undergoing radical cystectomy for bladder cancer. Detecting sarcopenia may assist in preoperative risk stratification and long-term management after radical cystectomy.

Effects of bipolar irreversible electroporation with different pulse durations in a prostate cancer mouse model.

Irreversible electroporation (IRE) is a non-thermal ablation technique for local tumor treatment known to be influenced by pulse duration and voltage settings, affecting its efficacy. This study aims to investigate the effects of bipolar IRE with different pulse durations in a prostate cancer mouse model. The therapeutic effectiveness was assessed with in vitro cell experiments, in vivo tumor volume changes with magnetic resonance imaging, and gross and histological analysis in a mouse model. The tumor volume continuously decreased over time in all IRE-treated groups. The tumor volume changes, necroptosis (%), necrosis (%), the degree of TUNEL-positive cell expression, and ROS1-positive cell (%) in the long pulse duration-treated groups (300 µs) were significantly increased compared to the short pulse duration-treated groups (100 µs) (all p < 0.001). The bipolar IRE with a relatively long pulse duration at the same voltage significantly increased IRE-induced cell death in a prostate cancer mouse model.

Effectiveness of Adjuvant Chemotherapy in Variant Histology Upper Tract Urothelial Carcinoma Following Radical Nephroureterectomy: Stabilized Inverse Probability Treatment Weighting Analysis of Single Center Experience.

PURPOSE: The study aimed to investigate the impact of adjuvant chemotherapy on time to recurrence (TTR) and overall survival (OS) in patients with histologic variants of upper tract urothelial carcinoma (VUTUC) following radical nephroureterectomy (RNU). MATERIALS AND METHODS: A retrospective review of 131 VUTUC patients' medical records, from a pool of 368 non-metastatic localized or locally advanced UTUC cases, treated at a single tertiary referral center between January 2011 and January 2021. The intervention was adjuvant chemotherapy administration post-RNU. TTR and OS were evaluated using Kaplan-Meier and Cox proportional hazard regression, covariates adjusted for age, postoperative GFR, history of neoadjuvant chemotherapy, T and N stage with stabilized inverse probability of treatment weighting (sIPTW). RESULTS: The application of adjuvant chemotherapy showed a significant extension in TTR (P = .01), but no substantial impact on OS (P = .19) after sIPTW adjustment for covariates. Multivariate analysis revealed adjuvant chemotherapy, tumor size, and lymphovascular invasion as significant prognostic factors for TTR. In contrast, only tumor size and perineural invasion were significant for OS. Adjuvant chemotherapy reduced the progression risk in certain VUTUC subtypes (squamous or glandular/micropapillary), but not in sarcomatoid variants. CONCLUSIONS: Adjuvant chemotherapy appears to improve TTR, albeit without a significant effect on OS, in nonmetastatic localized and locally advanced VUTUC patients post-RNU. While beneficial to some VUTUC subtypes, it did not yield significant advantages for sarcomatoid variants. Despite adjustments for known confounders, the study's findings may be subject to potential selection bias and unmeasured confounding factors.

Preoperative C-reactive protein to albumin ratio as a novel prognostic biomarker for the oncological outcomes of radical nephroureterectomy.

PURPOSE: This study aimed to evaluate the prognostic impact of the preoperative C-reactive protein to albumin ratio (CAR) on progression-free survival (PFS) and cancer-specific survival (CSS) in patients with upper urinary tract urothelial carcinoma (UTUC) undergoing radical nephroureterectomy (RNU). METHODS: A retrospective analysis was conducted using data from a single-center nephroureterectomy registry between January 2011 and December 2017. Participants were categorized into high and low CAR groups based on the optimal CAR cut-off value determined using the Youden index. The primary endpoint was PFS, the time from RNU to metastasis or disease recurrence. The secondary endpoint was CSS, the time from RNU to UTUC-related death. Median PFS and CSS were compared between the high and low CAR groups using Kaplan-Meier analysis and log-rank test. Multivariable Cox proportional hazard regression analysis was performed to assess the prognostic significance of CAR, adjusting for known prognostic factors. RESULTS: We included 491 patients with UTUC in the analysis. The optimal CAR cut-off value was determined to be 0.036, which resulted in classifying 49.3% (242/491) of patients into the high CAR group. The high CAR group had older patients (69.8 vs. 67.4, p-value = 0.01), advanced T and N stages (p-value<0.001), high-grade tumor (p-value = 0.03), and a higher incidence of preoperative hydronephrosis (p-value < 0.01) than the low CAR group. The high CAR group demonstrated significantly inferior median PFS (78.3 vs. 100.3 months, p-value < 0.01) and CSS (73.2 vs. 96.1 months, p-value < 0.01) than the low CAR group. Moreover, high CAR independently increased the risk of disease progression (hazard ratio [HR]: 1.80, 95% confidence interval [CI]: 1.23-2.64, p < 0.01) and UTUC-related mortality (HR: 1.79, 95% CI: 1.15, p < 0.01). CONCLUSION: Pre-operative CAR is independently associated with poor PFS and CSS in patients with UTUC undergoing RNU. Moreover, CAR may be an independent UTUC prognostic factor, offering a cost-effective and minimally invasive marker. However, further validation through large-scale, multi-center studies is necessary to confirm these findings and determine the optimal CAR cut-off value.

Clinical Significance of Radical Prostatectomy in Clinical Lymph Node Metastasis in Prostate Cancer.

BACKGROUND: This study aimed to investigate the role of radical prostatectomy (RP) among clinical nodal metastasis prostate cancer and whether histological confirmation of lymph node metastasis through surgery can help with treatment. PATIENTS AND METHODS: After excluding patients with distant metastatic prostate cancer or neoadjuvant androgen deprivation therapy, 42 patients with clinical nodal metastasis who underwent RP at our institution were included in the study. We classified them as having or not having pathological lymph node metastasis. Clinicopathologic data were analyzed in this retrospective chart review. Kaplan-Meier analysis was used to calculate the estimated castration-resistant prostate cancer (CRPC)-free survival, biochemical recurrence (BCR)-free survival, and cancer-specific survival (CSS). RESULTS: There is no significant difference in age, presence of diabetes mellitus, hypertension, BCR time, CRPC time, overall survival, salvage RT rate, and initial prostate-specific antigen level between the two groups. However, there is a significant difference in the pathology N1 group in terms of pathological T stage, pathologic Gleason score, BCR rate, CRPC rate, and CSS. A multivariate Cox proportional hazard regression analysis was used to identify predictors of CRPC-free survival. Patients with pathological lymph node metastasis had a shorter CRPC-free survival [hazard ratio (HR) 4.87; 95% confidence interval (CI) 1.25-19.00, p = 0.02]. CONCLUSION: Radical prostatectomy can confirm lymph node metastasis. Although pathologic diagnosis has no effect on time to BCR and CPRC, because it affects BCR rate, CRPC rate, and CSS, an accurate pathological diagnosis obtained through surgery is beneficial in the treatment of clinical lymph node metastasis prostate cancer.

A novel biguanide derivative, IM176, induces prostate cancer cell death by modulating the AMPK-mTOR and androgen receptor signaling pathways.

Background: Metformin and phenformin, biguanide derivatives that are widely used to treat type 2 diabetes mellitus, have recently been shown to exert potential anticancer effects in prostate cancer. This study compared the antiprostate cancer effects of the novel biguanide derivative IM176 with those of metformin and phenformin. Methods: Prostate cancer cell lines and patient-derived castration-resistant prostate cancer (CRPC) cells were treated with IMI76, metformin, and phenformin. The effects of these agents on cell viability, annexin V-FITC apoptosis, mammalian target of rapamycin inhibition, protein expression and phosphorylation, and gene expression were evaluated. Results: IM176 dose dependently reduced the viability of all prostate cancer cell lines tested, with IC50s (LNCaP: 18.5 µM; 22Rv1: 36.8 µM) lower than those of metformin and phenformin. IM176 activated AMP-activated protein kinase, inhibiting mammalian target of rapamycin and reducing the phosphorylation of p70S6K1 and S6. IM176 inhibited the expression of androgen receptor, the androgen receptor splice variant 7, and prostate-specific antigen in LNCaP and 22Rv1 cells. IM176 increased caspase-3 cleavage and annexin V-positive/propidium iodide-positive cells, which indicated apoptosis. Moreover, IM176 reduced viability, with low IC50, in cultured cells derived from two patients with CRPC. Conclusion: The antitumor effects of IM176 were comparable with those of other biguanides. IM176 may therefore be a novel candidate for the treatment of patients with prostate cancer, including those with CRPC.

DNA methylation biomarkers distinguishing early-stage prostate cancer from benign prostatic hyperplasia.

Background: DNA methylation markers are considered robust diagnostic features in various cancer types, as epigenetic marks are commonly altered during cancer progression. Differentiation between benign prostatic hyperplasia (BPH) and early-stage prostate cancer (PCa) is clinically difficult, relying on the information of the patient's symptoms or levels of prostate-specific antigen. Methods: A total of 42 PCa patients and 11 BPH patients were recruited. Genomic DNA was purified from tissues and used for the library preparation of the target-enriched methylome with enzymatic conversion and a Twist 85 Mbp EM-seq panel. Paired-end sequencing (150 bp) was performed using NovaSeq 6000 or NextSeq 550. After quality control, including adapter trimming and de-duplication of raw sequencing data, differential methylation patterns were analyzed between the BPH and PCa groups. Results: We report DNA methylation patterns existing between BPH and PCa. The major finding is that broad hypermethylation occurred at genic loci in PCa tissues as compared to the BPH. Gene ontology analysis suggested that hypermethylation of genic loci involved in chromatin and transcriptional regulation is involved in cancer progression. We also compared PCa tissues with high Gleason scores to tissues with low Gleason scores. The high-Gleason PCa tissues showed hundreds of focal differentially methylated CpG sites corresponding to genes functioning in cancer cell proliferation or metastasis. This suggests that dissecting early-to-advanced-grade cancer stages requires an in-depth analysis of differential methylation at the single CpG site level. Conclusions: Our study reports that enzymatic methylome sequencing data can be used to distinguish PCa from BPH and advanced PCa from early-stage PCa. The stage-specific methylation patterns in this study will be valuable resources for diagnostic purposes as well as further development of liquid biopsy approaches for the early detection of PCa.

Effect of decreased renal function on poor oncological outcome after radical cystectomy.

PURPOSE: To evaluate the impact of preoperative renal impairment on the oncological outcomes of patients with urothelial carcinoma who underwent radical cystectomy. MATERIALS AND METHODS: We retrospectively reviewed the medical records of patients with urothelial carcinoma who underwent radical cystectomy from 2004 to 2017. All patients who underwent preoperative 99mTc-diethylenetriaminepentaacetic acid renal scintigraphy (DTPA) were identified. We divided the patients into two groups according to their glomerular filtration rates (GFRs): GFR group 1, GFR≥90 mL/min/1.73 m²; GFR group 2, 60≤GFR<90 mL/min/1.73 m². We included 89 patients in GFR group 1 and 246 patients in GFR group 2 and compared the clinicopathological characteristics and oncological outcomes between the two groups. RESULTS: The mean time required for recurrence was 125.5±8.0 months in GFR group 1 and 85.7±7.4 months in GFR group 2 (p=0.030). The mean cancer-specific survival was 131.7±7.8 months in GFR group 1 and 95.5±6.9 months in GFR group 2 (p=0.051). The mean overall survival was 123.3±8.1 months in GFR group 1 and 79.5±6.6 months in GFR group 2 (p=0.004). CONCLUSIONS: Preoperative GFR values in the range of 60≤GFR<90 mL/min/1.73 m² are independent prognostic factors for poor recurrence-free survival, cancer-specific survival, and overall survival in patients after radical cystectomy compared with GFR values of ≥90 mL/min/1.73 m².

Clinical Utility of a 3D-Printed Patient-Specific Surgical Guide for Partial Nephrectomy.

Partial nephrectomy (PN) is a common surgery for small renal masses. The goal is to remove the mass completely while preserving renal function. A precise incision is, therefore, important. However, no specific method for surgical incision in PN exists, although there are several guides for bony structures using three-dimensional (3D) printing methods. Therefore, we tested the 3D printing method to create a surgical guide for PN. We describe the workflow to make the guide, which comprises computed tomography data acquisition and segmentation, incision line creation, surgical guide design, and its use during surgery. The guide was designed with a mesh structure that could be fixed to the renal parenchyma, indicating the projected incision line. During the operation, the 3D-printed surgical guide accurately indicated the incision line, without distortion. An intraoperative sonography was performed to locate the renal mass, which confirmed that the guide was well placed. The mass was completely removed, and the surgical margin was negative. No inflammation or immune reaction occurred during and 1 month after the operation. This surgical guide proved useful during PN for indicating the incision line and was easy to handle, without complications. We, therefore, recommend this tool for PN with improved surgical outcome.

Biopsy-Integrated 3D Magnetic Resonance Imaging Modeling of Prostate Cancer and Its Application for Gleason Grade and Tumor Laterality Assessment.

CONTEXT.­: Grade Group assessed using Gleason combined score and tumor extent is a main determinant for risk stratification and therapeutic planning of prostate cancer. OBJECTIVE.­: To develop a 3-dimensional magnetic resonance imaging (MRI) model regarding Grade Group and tumor extent in collaboration with uroradiologists and uropathologists for optimal treatment planning for prostate cancer. DESIGN.­: We studied the data from 83 patients with prostate cancer who underwent multiparametric MRI and subsequent MRI-transrectal ultrasound fusion biopsy and radical prostatectomy. A 3-dimensional MRI model was constructed by integrating topographic information of MRI-based segmented lesions, biopsy paths, and histopathologic information of biopsy specimens. The multiparametric MRI-integrated Grade Group and laterality were assessed by using the 3-dimensional MRI model and compared with the radical prostatectomy specimen. RESULTS.­: The MRI-defined index tumor was concordant with radical prostatectomy in 94.7% (72 of 76) of cases. The multiparametric MRI-integrated Grade Group revealed the highest agreement (weighted κ, 0.545) and a significantly higher concordance rate (57.9%) than the targeted (47.8%, P = .008) and systematic (39.4%, P = .01) biopsies. The multiparametric MRI-integrated Grade Group showed significantly less downgrading rates than the combined biopsy (P = .001), without significant differences in upgrading rate (P = .06). The 3-dimensional multiparametric MRI model estimated tumor laterality in 66.2% (55 of 83) of cases, and contralateral clinically significant cancer was missed in 9.6% (8 of 83) of cases. The tumor length measured by multiparametric MRI best correlated with radical prostatectomy as compared with the biopsy-defined length. CONCLUSIONS.­: The 3-dimensional model incorporating MRI and MRI-transrectal ultrasound fusion biopsy information easily recognized the spatial distribution of MRI-visible and MRI-nonvisible cancer and provided better Grade Group correlation with radical prostatectomy specimens but still requires validation.

Effects of different applied voltages of irreversible electroporation on prostate cancer in a mouse model.

As a non-thermal ablation method, irreversible electroporation (IRE) has been widely investigated in the treatment of prostate cancer. However, no consensus has been achieved on the optimal parameters of IRE for prostate cancer. Since high voltage is known to carry risks of muscle contraction and patient discomfort, it is crucial to identify the minimum but effective and safer applied voltage to inhibit tumor growth. In this study, the effect of different applied voltages of IRE on prostate cancer was evaluated in BALB/c nude mice. Mathematical simulation and measurement of the actual ablation area revealed a larger ablation area at a higher voltage. In in vivo experiment, except for the three different voltages applied, all groups received identical electrical conditions: pulse number, 180 (20 groups × 9 pulses/group); pulse width, 100 µs; pulse interval, 2 ms; distance between the electrodes, 5 mm; and electrode exposure length, 15 mm. Whilst the tumor volume initially decreased in the 500 V (1000 V/cm) and 700 V (1400 V/cm) groups and subsequently increased, only a transient increase followed by a continuous decrease until the sacrifice was observed in the 900 V (1800 V/cm) group. This result demonstrated a lasting effect of a higher applied voltage on tumor growth inhibition. The histological, immunohistochemical, and western blot findings all confirmed IRE-induced apoptosis in the treatment groups. Taken together, 900 V seemed to be the minimum applied voltage required to reduce tumor growth, though subsequent studies are anticipated to further narrow the voltage intervals and lower the minimum voltage required for tumor inhibition.

The usefulness and ergonomics of a new robotic system for flexible ureteroscopy and laser lithotripsy for treating renal stones.

PURPOSE: To investigate the usefulness and ergonomics of a newly developed robotic system for flexible ureteroscopy (easyUretero). MATERIALS AND METHODS: During in vitro testing, six participants performed renal stone removal four times in an artificial kidney-ureter-bladder model. Each participant manipulated a single-use digital flexible ureteroscope (LithoVue) with their hands and the robotic system, sequentially. We compared the task completion times of each participant. The ergonomics of and operational satisfaction with each procedure were assessed by questionnaires. In vivo tests evaluated the operability and safety of the robotic system in two live female pigs. We checked that all the steps of flexible lithotomy for renal stones could be completed individually. RESULTS: The task completion time with the robotic system during in vitro testing was significantly longer than with manual ureteroscopy regardless of the operator's competence level (expert professors: 282.6±92.4 seconds vs. 73.6±43.3 seconds, p<0.001; fellows: 247.5±57.7 seconds vs. 95.8±43.7 seconds, p<0.001; residents: 281.3±111.0 seconds vs. 188.6±138.6 seconds, p<0.001). The residents took more time to remove the upper and mid caliceal stones with the robotic system. The ergonomic evaluation was better for the robotic system, but operational satisfaction was lower, and there was no statistical difference among the groups. In vivo tests showed that all the steps of robotic flexible ureteroscopy could be completed without difficulty. No safety issues were encountered during the procedure. CONCLUSIONS: The robotic system (easyUretero) was ergonomic and safe for flexible ureteroscopy and laser lithotripsy for renal stones.

A Comparative Analysis of Robot-Assisted Laparoscopic Pyeloplasty in Pediatric and Adult Patients: Does Age Matter?

We investigated factors that affect the surgical outcomes of robotic pyeloplasty by comparing the surgical results of pediatric and adult patients with ureteropelvic junction stricture (UPJO). We retrospectively reviewed patients who underwent robotic pyeloplasty for UPJO between January 2013 and February 2022. The patients were categorized into two groups: the pediatric (≤18 years) and adult (>18 years) groups. The perioperative and postoperative outcomes and surgical complications were comparatively analyzed. Prognostic factors for predicting surgical failure were analyzed with multivariable logistic regression analysis. The pediatric group showed longer total operation and console times. The mean pain score was lower in the pediatric group than in the adult group on days 1 and 2 after surgery. The average amount of morphine used in the pediatric group was lower during postoperative days 0−2. No differences in the length of hospital stay, incidence of surgical failure, and incidence of urolithiasis requiring treatment after robotic pyeloplasty were observed between the groups. The only factor that predicted surgical failure was a history of urolithiasis before surgery. The results showed that age did not affect the surgical outcome.

High-Frequency Pulsed Electric Field Ablation in Beagle Model for Treatment of Prostate Cancer.

Conventional irreversible electroporation (IRE) with low-frequency pulsed electric field (LF-PEF) is used to induce cell death; however, it has several disadvantages including a long procedure time and severe muscle contraction due to high-voltage electric field. This study investigates a novel IRE protocol with high-frequency pulsed electric field (HF-PEF) of 500 Hz repetition to ablate the prostate tissue in beagles for treatment of prostate cancer. A finite element analysis was performed to validate optimal electrical field strength for the procedure. In total, 12 beagles received HF-PEF of 500 Hz and were sacrificed at 4 h, 4 days, and 28 days (3 each). The remaining three beagles underwent sham procedure. The outcomes of HF-PEF were assessed by histological responses. HF-PEF successfully decellularized the prostate tissues 4 h after the treatment. The prostate glands, duct, and urethra were well preserved after IRE with HF-PEF. The ablated prostatic tissues were gradually regenerated and appeared similar to the original tissues 28 d after IRE with HF-PEF. Moreover, electrocardiography and hematology demonstrated that IRE with HF-PEF did not seriously affect the cardiac tissue. HF-PEF was effective and safe in the beagle prostate and effectively induced the ablation and gradually recovered with cellular regeneration.

Comparative oncological outcomes after radical prostatectomy or external beam radiation therapy plus androgen deprivation therapy in men with clinical T3b prostate cancer.

OBJECTIVE: To compare oncological outcomes in men with clinical T3b prostate cancer who underwent radical prostatectomy or a combination of radiation therapy plus androgen deprivation therapy. METHODS: Men with clinical T3b prostate cancer who underwent radical prostatectomy or radiation therapy plus androgen deprivation therapy between 2007 and 2014 were evaluated. All patients were relatively healthy, with Eastern Cooperative Oncology Group performance status of 0 or 1 without nodal or distant metastasis. Cancer-specific survival was analyzed. Age, Charlson Comorbidity Index, biopsy Gleason score and pretreatment prostate-specific antigen were adjusted by propensity score matching. The Cox proportional hazards model was used to assess factors prognostic of cancer-specific survival. RESULTS: Of the 152 patients with clinical T3b prostate cancer, 45 underwent radical prostatectomy, and 107 underwent radiation therapy plus androgen deprivation therapy between 2007 and 2014. The mean cancer-specific survival was significantly longer in the radical prostatectomy than in the radiation therapy plus androgen deprivation therapy group (P = 0.029). Age, Charlson Comorbidity Index and pretreatment prostate-specific antigen were significantly higher in the radiation therapy plus androgen deprivation therapy group. In the propensity score matched population of 24 patients each, the median cancer-specific survival remained significantly longer in the radical prostatectomy than in the radiation therapy plus androgen deprivation therapy group (not reached vs 112.93 ± 11.94 months, P = 0.026). Multivariate analysis showed that undergoing radiation therapy plus androgen deprivation therapy was the only significant poor prognostic factor for cancer-specific survival (hazard ratio 6.694, 95% confidence interval 1.642-27.592, P = 0.008). CONCLUSION: Cancer-specific survival was significantly longer in men with clinical T3b prostate cancer who underwent radical prostatectomy than radiation therapy plus androgen deprivation therapy, suggesting that radical prostatectomy can be a better treatment option for the initial definitive treatment for these patients.

The lymphocyte/monocyte ratio and red blood cell transfusion during radical retropubic prostatectomy.

PURPOSE: Despite improvements of strategy in radical retropubic prostatectomy, blood loss is still a major concern. The lymphocyte/monocyte (LM) ratio is a prognostic indicator for various diseases. We identified the risk factors, including the LM ratio, for red blood cell (RBC) transfusion during radical retropubic prostatectomy. METHODS: This retrospective study assessed patients who underwent radical retropubic prostatectomy between March 2009 and December 2020. To determine the risk factors for RBC transfusion, a multivariate logistic regression analysis was conducted. A receiver operating characteristic (ROC) curve analysis was also performed. Postoperative outcomes, including acute kidney injury (AKI), hospitalization duration, and intensive care unit (ICU) admission, were also evaluated. RESULTS: Among 1302 patients, 158 patients (12.1%) received an intraoperative RBC transfusion. Multivariate logistic regression analysis demonstrated that the risk factors for RBC transfusion were the LM ratio, hemoglobin, 6% hydroxyethyl starch amount, and positive surgical margin. The area under the ROC curve of LM ratio was 0.706 (cut-off = 4.3). The LM ratio at ≤ 4.3 was significantly related to transfusion in multivariate-adjusted analysis (odds ratio = 4.598, P < 0.001). AKI and ICU admission were significantly higher, and the hospitalization duration was significantly longer in patients with RBC transfusion. CONCLUSIONS: The LM ratio was a risk factor for RBC transfusion in radical retropubic prostatectomy. The optimal cut-off value of the LM ratio to predict transfusion was 4.3. RBC transfusion was associated with poor postoperative outcomes. Therefore, our results suggest that the LM ratio provide useful information on RBC transfusion in radical retropubic prostatectomy.

Impact of preoperative chemotherapy on pathologic nodal status in muscle-invasive bladder cancer: optimal lymphadenectomy in the preoperative chemotherapy era.

PURPOSE: To investigate the impact of preoperative chemotherapy (pCTX) on pathologic nodal (pN) status and evaluate the optimal lymphadenectomy method according to clinical nodal (cN) status in patients with muscle-invasive bladder cancer who received pCTX. MATERIALS AND METHODS: We retrospectively reviewed 449 patients with muscle-invasive bladder cancer who underwent radical cystectomy. Among them, 139 (31.0%) received pCTX. We analyzed overall survival among three groups (cN-pCTX-, cN-pCTX+, and cN+pCTX+); the impact of lymphadenectomy extent according to the history of pCTX in cN- patients (n = 393); and the pN status which includes number of positive lymph nodes, and lymph node density in cN- patients who underwent extended lymphadenectomy (n = 222). RESULTS: Overall survival was significantly dependent on cN status, and pCTX had no survival advantage although it decreased the percentage of pN+ patients and the number of positive lymph nodes in cN- patients. Lymph node density showed a significant prognostic effect on overall survival in Cox regression analysis both in cN- and cN+ patients. In cN- patients, there was no significant survival difference according to lymphadenectomy extent regardless of receiving pCTX. CONCLUSIONS: pCTX can control micrometastases but not overt metastases, despite decreasing the number of positive lymph nodes in patients with muscle-invasive bladder cancer. Although extended lymphadenectomy is a reasonable diagnostic strategy in the pCTX era, standard dissection is as therapeutic as extended dissection in patients with cN- disease.

Biopsy-detected Gleason grade 5 tumor is an additional prognostic factor in metastatic hormone-sensitive prostate cancer.

PURPOSE: A Gleason score ≥ 8, metastatic tumor burden, and visceral metastasis are known prognostic factors for patients with metastatic hormone-sensitive prostate cancer (mHSPC). Notably, however, these indicators have not been fully validated internationally. We aimed in this present study to further analyze the factors that influence the prognosis of mHSPC. METHODS: In this retrospective study, we identified 201 patients with newly diagnosed mHSPC between 2008 and 2014 and collected their clinical information. Cox proportional hazard regression models were used to identify prognostic factors in mHSPC. RESULTS: The mean age of the patients at presentation was 70 years (interquartile range (IQR), 64-76 years). The prostate-specific antigen level was 141 ng/mL (IQR, 58.8-464.5 ng/mL). Of the 201 study patients, 191 (94.5%) and 131 (65.2%) cases had a biopsy Gleason score ≥ 8 and grade 5, respectively. More than 4 metastases were detected in 134 patients. Castration-resistant prostate cancer (CRPC) was evident in 160 cases after a mean follow-up period of 46.6 months. By multivariable analysis, a Gleason grade of 5 and bone metastasis lesion count ≥ 4 were found to be significantly associated with CRPC-free survival (hazard ratio (HR), 1.45; 95% confidence interval (CI), 1.01-2.07) and (HR 2.02; 95% CI 1.39-2.92) and overall survival (HR 1.67 95%; CI 1.16-2.42) and (HR 1.67 95%; CI 1.16-2.41). CONCLUSIONS: Bone metastases ≥ 4 and a Gleason grade 5 are independent prognostic factors for CRPC-free and overall survival in mHSPC. A Gleason grade 5 is therefore a new prognostic indicator in mHSPC.